Summary of Work: The research on genetic susceptibility tests the hypothesis that commonly inherited allelic variants of certain genes, in conjunction with environmental exposures, affect a person's risk of developing disease. The primary focus of this work has been on bladder cancer, although recently we have expanded to include studies of prostate cancer and, in collaboration with Stephanie London, lung cancer. Progress in the last year includes the following. Bladder cancer: through a contract with UNC we have obtained polymorphism data for the H- ras VNTR polymorphism on over 400 cases and controls enrolled in the bladder cancer study. Analysis of this data is just beginning. Prostate cancer: through collaboration with researchers at Bowman Gray we have obtained DNA samples with linked epidemiologic information with which to extend our finding of an association between a polymorphism in the 3'UTR of the vitamin D receptor gene and prostate cancer risk. Genotyping has been completed and data analysis is to begin. In addition, in collaboration with Dr. Bell we have genotyped prostate cancer cases and controls from our original prostate cancer study for a polymorphism in CYP17, a gene involved in androgen metabolism, and are starting data analysis. Lung cancer: Using Dr. London's case-control study of lung cancer we have completed a study of a polymorphism in the myeloperoxidase gene. Lung tissue has high levels of myleoperoxidase which is known to activate certain tobacco smoke carcinogens and we show that the polymorphism, which destroys an SP1 promoter site, has a protective effect on lung cancer risk. This manuscript has just been submitted for publication. Finally, I have been working to develop the Institute's Environmental Genome Project which proposes to identify allelic variants of 200 or more environmentally-important genes in a population-based sample of the U.S. population and to develop subsequent functional and epidemiologic studies exploring the environmental and genetic determinants of disease risk.